Mini-dose glucagon study

Recently the results of a mini-dose glucagon study by Xeris Pharma were published. Their goal was to prevent exercise-induced hypoglycemia, but if this mini-dose product reaches the market, we can repurpose it for other situations, right? :wink:

Original paper: Summary or Full article (PDF)

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You can do this now. The product is available.

Xeris pharmaceuticals make Gvoke glucagon, which is the shelf-stable glucagon that does not need to be mixed before injecting.

It comes in a 1 mg dose which is contained in 0.20 ml of liquid volume. (Thatā€™s the same volume that is 20 units of insulin, to help visualize it.)

So the only thing you need to be able to do is reduce the amount you are injecting. Thatā€™s easy. You inject the whole thing into an empty vial (easy and cheap to buy), and then use a syringe and just draw out a small amount.

The amount used in the study would be the same as using 3 units from an insulin syringe.

If you want to try this, buy some empty vials and get some insulin syringes. I can send you the glucagon, I have a bunch.

PM me your address and Iā€™ll send you some. :+1:

EDIT:
Actually, scratch the buying of vials and syringes. My gosh, I have a million sterile vials and syringes. I can send you everything!

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Unrelated to my comment above, looking at the study, here is what they did:

Treatment arm A - taking glucagon immediately before exercise and reducing basal
Treatment arm B - taking a placebo
Treatment arm C - taking glucagon without reducing basal




Okay class, time for a quick quiz. What is the obvious thing missing?!?



If you said ā€œreducing basal and taking carbs immediately before exerciseā€, step to the front of the class, you are an A+ student!

Itā€™s silly to not use that as a comparison in the study. Taking carbs will be much better for exercise performance than taking glucagon.

[sigh]

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@Eric Thanks for stating what I hope many of us were thinking, ā€œWhy not do the natural thing and just eat some food prior to or during exercise?ā€ While I appreciate the inventiveness of using glucagon and Iā€™m sure it has its place in several situations (a dual drug T1/T2 treatment device?), seems the natural thing is to eat an appleā€¦vice paying for more drugs, injecting them, and further enriching big pharmaā€¦natural foods have to better for us.

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I did have that same reaction, but as this thread evolved I got excited about the potential of this liquid stuff for a glucagon pump - or a combination insulin / glucagon pump that can automatically dose to keep a T1 in range.

It is interesting, as @eric points out, that the most obvious and effective alternative treatment is not one of the conditions. A great example of institutional bias.

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From an exercise performance standpoint, glucagon has a negative effect. Glucagon inhibits glycolysis, which is one of the ways our body produces energy.

The body is smart. It says, ā€œHey low blood sugar, we need to prioritize releasing more glucose into the blood to raise BG instead of using it to create energy right nowā€¦ā€

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I wonder if this is just intended for excersise?

I become a little nauseous with low BGs. I tend to eat meals with a lot of fiber. When Iā€™ve dosed a bit too much for these meals the glucose takes much longer to kick in. These have been my most stressful lows. I would really like a injection instead of liquid that im trying not to throw up.

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Does it follow that small glycogen doses would be useful when thereā€™s extra insulin floating around due to having to send the number plummeting after a high BG as opposed to having to take a bunch of carbs and potentially gaining weight? Would there be any anti-exercise effects beyond the period where it was being used?

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Yes, it would be a benefit for someone who was watching their calorie intake.

I was speaking simply of the performance side of it. Carbs vs glucagon.

No, itā€™s fine when you are not exercising, or exercising at a lower intensity.

But I will say that if you donā€™t have sufficient glycogen stores, this is dangerous for people because they think itā€™s going to raise their BG but it wonā€™t. If your liver stores are empty, glucagon does you no good.

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No, this was not meant just for exercise. Itā€™s meant for treatment of severe low BG.

The people who did the study are just trying to examine other possible uses.

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Good Idea @Eric ,

But sometimes in order to do a proper scientific study, you may be trying to simulate a specific conditionā€¦ and the fact that many (myself included) find taking carbs right before exercise impacts my willingness to ā€œpushā€, as well as may also impede certain goals of the routine.

Add to thatā€¦ it also depends on the Goal of the study (and backing Thesis) which may at times be constrained by a sponsor or other Rules of Engagement sort of speak.

For those trying to get to the paper (And getting an error)

Try these links here:
via DiabetesJournals Original PDF and the Full Article
via ResearchGate Enhanced PDF

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Good to know thank you. Iā€™m more confident when it comes to understanding protein whereas with aerobic activities I mostly just schedule them without ever getting particularly scientific.

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Thanks! Iā€™ll update my post.

I seem to recall a couple years ago that there was a closed loop system pump in trials that had two cartridges, one with insulin and the other with glucagon.

Mike

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I have a vague memory of something like this as well.

b

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I reference iLet pump which is in development. Here is a paper on 2 different such pumps.
https://clinicaltrials.gov/ct2/show/NCT04053712

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If I recall correctly, the iLet pump has been in development for the past 15 years. :joy:

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Itā€™s a wicked hard problem. Itā€™s one of the reasons why I think Tandemā€™s incremental approach is brilliant. Small steps ā€¦ adjacent possible.

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Thereā€™s also Inreda Diabetic in the Netherlands developing a dual-hormone artificial pancreas. They expect to launch their product on the Dutch market in 2024, FWIW.

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